The basic objective of this proposal is to identify antimicrobial agents which will be of use in the control and treatment of destructive periodontal diseases. The specific aims are as follows: (a) to determine the antibiotic susceptibilities of bacteria associated with periodontally diseased sites, (b) to determine the concentrations achieved and maintained in gingival fluid following oral administration of certain antibiotics, and (c) to relate the antibiotic levels available in the gingival fluid to the susceptibilities of periodontal bacteria as a means of determining the expected effect of an antibiotic on the periodontal microbiota. Susceptibility profiles will be determined by using a sufficent number of representative strains of different bacterial species to obtain a profile of the susceptibilities of the species to the antibiotics tested. The bacterial species to be tested either are currently implicated as possible etiologic agents of destructive periodontal diseases or else are frequently associated with periodontally diseased sites. The minimal inhibitory concentrations of the following antibiotics: ampicillin, amoxicillin, amoxicillin/clavulanic acid, clindamycin, doxycycline, minocycline, metronidazole, tetracycline, and erythromycin, will be determined for a significant number of strains for each species by agar dilution techniques. These data will be used to evaluate the inhibitory effects of different antimicrobial agents against specific bacteria implicated or associated with destructive periodontal diseases. Gingival fluid levels will be measured following administration of recommended oral dosages of metronidazole, clindamycin, doxycycline, and amoxicillin/clavulanic acid to determine the concentrations achieved and maintained at the site of periodontal infection. These levels will be related to the MICs of these antibiotics to determine which organisms can be expected to be inhibited, in vivo, by the antibiotic at concentrations readily available in the periodontal pocket following a recommended oral dosage regimen.